Riediger Thomas, Traebert Martin, Schmid Herbert A, Scheel Caroline, Lutz Thomas A, Scharrer Erwin
Institute of Veterinary Physiology, University of Zurich, Winterthurerstrasse 260, 8057, Zurich, Switzerland.
Neurosci Lett. 2003 May 1;341(2):151-5. doi: 10.1016/s0304-3940(02)01381-2.
The recently discovered hormone ghrelin, which is secreted from the stomach during fasting and hypoglycemia opposes the homeostatic functions of leptin by increasing food intake and decreasing energy expenditure. The hypothalamic arcuate nucleus (Arc) mediates the effects of leptin and contains a high density of ghrelin receptors. The leptin- and ghrelin-responsive network involves the hypothalamic neuropeptide Y/alpha-melanocyte stimulating hormone (NPY/alpha-MSH) system. In the rat, neurons expressing the orexigenic peptide NPY are mainly located in the ventromedial Arc (ArcM), while pro-opiomelanocortin (POMC) neurons, synthesizing the anorectic peptide alpha-MSH, predominate in the ventrolateral Arc (ArcL). In extracellular single unit recordings from in vitro slice preparations of the Arc, superfusion of ghrelin (10(-8) M) exerted predominantly excitatory effects on ArcM neurons (73%, n=93), while a high number ArcL neurons were inhibited in response to ghrelin (42%, n=43). The excitatory effect of ghrelin on neuronal activity was postsynaptic since it was unaffected by synaptic blockade (low Ca(2+)/high Mg(2+) solution). In contrast, the inhibitory response in the ArcL was abolished by the blockade of synaptic interactions indicating a presynaptic mechanism. These results indicate that circulating ghrelin may oppose the actions of leptin by directly activating NPY-neurons of the ArcM and by indirectly inhibiting POMC neurons of the ArcL.
最近发现的激素胃饥饿素在禁食和低血糖期间由胃分泌，它通过增加食物摄入量和减少能量消耗来对抗瘦素的稳态功能。下丘脑弓状核（Arc）介导瘦素的作用，并且含有高密度的胃饥饿素受体。瘦素和胃饥饿素反应网络涉及下丘脑神经肽Y/α-黑素细胞刺激素（NPY/α-MSH）系统。在大鼠中，表达促食欲肽NPY的神经元主要位于腹内侧弓状核（ArcM），而合成厌食肽α-MSH的阿黑皮素原（POMC）神经元在腹外侧弓状核（ArcL）中占主导地位。在Arc体外脑片制备的细胞外单单位记录中，灌注胃饥饿素（10^(-8) M）对ArcM神经元主要产生兴奋作用（73%，n = 93），而大量ArcL神经元对胃饥饿素产生抑制反应（42%，n = 43）。胃饥饿素对神经元活动的兴奋作用是突触后性的，因为它不受突触阻断（低钙/高镁溶液）的影响。相反，ArcL中的抑制反应通过突触相互作用的阻断而消除，表明是一种突触前机制。这些结果表明，循环中的胃饥饿素可能通过直接激活ArcM的NPY神经元和间接抑制ArcL的POMC神经元来对抗瘦素的作用。
